Stereochemistry of water addition in triterpene synthesis: The structure of arabidiol

Organic Letters

Volumn 9, Issue 11, 2007, Pages 2183-2186

  Kolesnikova, Mariya D ^a   Obermeyer, Allie C ^a   Wilson, William K ^a   Lynch, David A ^a   Xiong, Quanbo ^a   Matsuda, Seiichi P T ^a  

^a RICE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARABIDIOL; TRITERPENE; UNCLASSIFIED DRUG; WATER;

ARABIDOPSIS; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; ENZYMOLOGY; SYNTHESIS;

ARABIDOPSIS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; TRITERPENES; WATER;

EID: 34250682615     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol070709b     Document Type: Article

References (21)

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7. 2 at room temperature.
8. Molecular modeling was done with Gaussian software: Frisch, M. et al. Gaussian 03, revision D.01; Gaussian, Inc.: Wallingford, CT, 2005. The full reference is given in the Supporting Information.
9. Fazio, G. C.; Xu, R.; Matsuda, S. P. T. J. Am. Chem. Soc. 2004, 126, 5678-5679. The correct structure of 5 was shown, but the systematic name was given incorrectly as (3S,13S,14R)-malabarica-8,17,21- trien-3-ol.
10. Matsuda, S. P. T.; Wilson, W. K.; Xiong, Q. Org. Biomol. Chem. 2006, 4, 530-543.
11. Rotation about the C13-C14 bond can occur only in the direction that places the substrate side chain in the distal position. See: Lodeiro, S.; Wilson, W. K.; Shan, H.; Matsuda, S. P. T. Org. Lett. 2006, 8, 439-442.
12. Analogous logic for tetracycles: Xiong, Q.; Rocco, F.; Wilson, W. K.; Xu, R.; Ceruti, M.; Matsuda, S. P. T. J. Org. Chem. 2005, 70, 5362-5375.
13. Although the absence of 5 (Figure 1) suggests that water attacks 7 before 7a can form, our mechanistic analysis includes 7a for completeness.
14. The ordered water that hydroxylates 7 is evidently inside the activesite cavity, where it may disrupt substrate folding to form the atypical 13S tricyclic cation 7 and thus prevent D-ring formation. Failure to replenish this water may result in cation 6, the precursor of 4 and other olefins.
15. The Supporting Information contains stereoviews and detailed analyses for these and other major structural types, including the dammarenyl cation.
16. Only (20S)-9 is common in nature, but dammar resin contains both C20 epimers: Mills, J. S.; Werner, A. E. A. J. Chem. Soc. 1955, 3132-3140.
17. 8: (a) Hoshino, T.; Sato, T. Chem. Commun. 2002, 291-301. 9:
18. (b) Tansakul, P.; Shibuya, M.; Kushiro, T.; Ebizuka, Y. FEBS Lett. 2006, 580, 5143-5149. The structures of 10 and 11 do not reveal the orientation of cation hydration. The orientation for 10 was deduced by isotopic labeling:
19. (c) Kushiro, T.; Hoshino, M.; Tsutsumi, T.; Kawai, K.-i.; Shiro, M.; Shibuya, M.; Ebizuka, Y. Org. Lett. 2006, 8, 5589-5592. We determined the orientation for 11 from NMR calculations (see the Supporting Information) and isotopic labeling experiments:
20. (d) Hoshino, T.; Nakano, S.; Kondo, T.; Sato, T.; Miyoshi, A. Org. Biomol. Chem. 2004, 2, 1456-1470.
21. The predominance of deprotonation over hydroxylation is augmented by the nature of cyclase active sites, which contain a number of hydrophobic residues and few ordered waters: Wendt, K. U. Angew. Chem., Int. Ed. 2005, 44, 3966-3971 and references therein.